Acute lung injury (ALI) has a high mortality despite sophisticated care. Recovery from ALI requires re-epitheliazation for the denuded alveolar basement membrane by adhesin and migration of proliferating type II cells on the provisional matrix. Integrins, probably play a key role in this repair, based on data in other cell types that injury increases both migration on provisional matrix and integrin expression. I hypothesize that (1) injury alters type II cell adhesion and migration on provisional matrix proteins; (2) changes in integrin expression or utilization mediate these functions; and (3) up-or down-regulation of specific integrins may augment or diminish alveolar epithelial cell adhesion and migration, and thus modulate alveolar repair. Using rat primary II cells and an alveolar epithelial cell line (MP48) that are injured by exposure to hyperoxia, I will determine how injury affects adhesion, migration, and integrin expression. Then I will overexpress or decrease integrin expression or specific integrins that are altered by injury and determine if this augments or inhibits alveolar re-epitheliazation. The long term goal of this project is to understanding the mechanisms of alveolar epithelial repair to permit therapeutic interventions that speed the recovery from ALI. This project will increase my knowledge of cellular and molecular biology. Specific techniques learned will include: video microscopic analysis of cell migration: northern blotting; cell transfection and gene transfer technology; use of antisense and dominant negative mutation strategies. My long term career goal is to become an independent investigator in academic Pulmonary Medicine.